Laatikainen, Lilja Elisa
(2009)
Signaling pathways and mechanism of action of the extracellular superoxide dismutase, SOD3.
[Tesi di dottorato]
(Inedito)
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
Signaling pathways and mechanism of action of the extracellular superoxide dismutase, SOD3 |
| Autori: |
| Autore | Email |
|---|
| Laatikainen, Lilja Elisa | lilja.laatikainen@utu.fi |
|
| Data: |
30 Novembre 2009 |
| Numero di pagine: |
164 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Biologia e patologia cellullare e molecolare "L. Califano" |
| Scuola di dottorato: |
Medicina molecolare |
| Dottorato: |
Oncologia ed endocrinologia molecolare |
| Ciclo di dottorato: |
22 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Vecchio, Giancarlo | [non definito] |
|
| Tutor: |
| nome | email |
|---|
| Castellone, Maria Domenica | [non definito] | | Santoro, Massimo | masantor@unina.it | | Laukkanen, Mikko O. | mikko.laukkanen@utu.fi |
|
| Data: |
30 Novembre 2009 |
| Numero di pagine: |
164 |
| Parole chiave: |
SOD3, inflammation, proliferation, thyroid, goiter |
| Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/04 - Patologia generale |
[error in script]
[error in script]
| Depositato il: |
28 Mag 2010 08:11 |
| Ultima modifica: |
30 Apr 2014 19:39 |
| URI: |
http://www.fedoa.unina.it/id/eprint/3946 |
| DOI: |
10.6092/UNINA/FEDOA/3946 |
Abstract
Reactive oxygen species (ROS) and especially hydrogen peroxide (H2O2) have been implicated in a multitude of cellular events ranging from pathogen eradication to finely tuned intracellular signal transduction under normal and pathological conditions. In some organs, such as thyroid gland, or in tissue injuries their expression is naturally high and requires special measures to keep it under control. Extracellular superoxide dismutase (SOD3) is an antioxidative enzyme, which converts superoxide into H2O2 thus reducing the harmful ROS burden of injured tissues. Recently, a more versatile role for SOD3 as an anti-inflammatory and signal modulating agent has begun to emerge. We studied the mechanism of action of SOD3 in tissue injury recovery and whether it has a role in the thyroid gland physiology and pathophysiology, which untill now have remained uncharacterized. We performed an adenovirally mediated gene transfer of SOD3 into rat hind limb and mouse peritoneum to assess its effect on tissue recovery and leukocyte migration. Our rat hind limb ischemia model provided an acute ischemic injury to study the effects of therapeutic molecules on the initiation of inflammation. A mouse peritonitis model allowed a more specific analysis of the infiltrating inflammatory cell subtypes. We also determined the expression of SOD3 and its influence on thyrocyte function from rat and human thyroid tissues and cell lines. SOD3 gene transfer markedly reduced the inflammatory cell accumulation into the rat hind limbs and the mouse peritonea as well as improved rat muscle tissue recovery. Interestingly, SOD3 seemed to have a pronounced effect on the macrophage population. Activation of the Ras-mitogen activated protein kinase (MAPK) pathway was upregulated whereas the expression of several inflammatory cytokines and cell adhesion molecules was downregulated. The SOD3 expression analysis and signal transduction studies on thyroid revealed high thyrotropin mediated SOD3 expression in normal rat thyroid and even higher in hyperproliferative goitrous tissue. Accordingly, silencing of SOD3 by small interfering RNA reduced thyrocyte proliferation. However, thyroid cancer tissue from human patients and rat thyroid cancer cell lines had significantly lower SOD3 expression. These studies describe a novel role for SOD3 in cell proliferation in injured tissue and in the thyroid gland physiology. Additionally, they elucidate the anti-inflammatory mechanism of SOD3. Thus, SOD3 could have therapeutic value in treatment of ischemic injuries, and in assessment of the degree of malignancy in thyroid hyperproliferative disorders.
Downloads per month over past year
Actions (login required)
 |
Modifica documento |
